Design: open-label, randomised, non-inferiority phase 2b trial with six arms, 36-month follow-up
Population: 450 Bolivian adults aged 18-50 with chronic indeterminate or early cardiac Trypanosoma cruzi infection
Primary outcome: sustained parasitological clearance on serial quantitative PCR to 36 months
Effect: 94% vs 95% for 30-day vs 60-day benznidazole (risk difference -2.0, 97.5% CI -5.41 to 1.45); adverse events 37% vs 60%

TESEO enrolled 450 adults aged 18 to 50 at three Bolivian sites with chronic Trypanosoma cruzi infection, indeterminate or early cardiac form, confirmed serologically and by quantitative PCR. Six arms compared benznidazole and nifurtimox at standard, shortened and extended schedules, with sustained parasitological clearance over 36 months as the primary outcome.

All four experimental regimens were non-inferior to their own standard of care at a -9.5 percentage-point margin. Benznidazole 150 mg once daily for 30 days cleared 94% against 95% on the 60-day twice-daily standard, a risk difference of -2.0 (97.5% CI -5.41 to 1.45). The toxicity difference is where the trial earns its keep: 37% had a drug-related adverse event on the 30-day regimen against 60% on the standard, a fall of 23 percentage points (95% CI -38 to -7). No other comparison reached significance.

One mechanistic observation travels beyond Chagas. Adverse events appeared within 10 to 14 days regardless of how long treatment was planned to run, which argues for idiosyncratic rather than cumulative toxicity - and therefore that the first fortnight is where monitoring belongs. This is phase 2b, open-label, in one country and one parasite population; the authors call for phase 3 work across genotypes before guidelines change.

Concentrate toxicity monitoring in the first 10-14 days of benznidazole, whatever the planned course.
Guidelines have not changed; the standard 60-day regimen remains what they recommend.
Halving both dose frequency and duration preserved 36-month parasitological clearance in this trial.
Nifurtimox arms were also non-inferior but showed no tolerability advantage.
Open-label, single-country phase 2b - parasite genotype varies by region and was not tested here.

Why it matters

Treatment interruption from toxicity is the main reason chronic Chagas goes untreated, and this halves the exposure without measurably costing clearance.

The statistics, in plain English

Non-inferiority means only that the shorter regimen is not worse by more than a prespecified margin - here 9.5 percentage points - and the confidence intervals sit comfortably inside it. That is a claim about not losing efficacy, not a claim of equivalence. The tolerability difference, by contrast, is a straightforward superiority finding with a confidence interval well away from zero, and it is the result most likely to survive replication.